This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Specific Aim 1, which previously assumed a single proposed secondary structure for MTB Thi C as a translational riboswitch. We now aim to determine secondary structure models for the "ON" and "OFF" states of the Thi C riboswitch through SHAPE probing (described below). Combined with transcriptional and translational assays being developed in collaboration with our colleagues at the Hansen's Disease lab, we aim to determine whether MTB Thi C expression is controlled transcriptionally of translationally through the upstream riboswitch sequence. Specific Aim 2 Our second specific aim is to obtain novel "hit" compounds with weak affinity for the ON and/or OFF state of the TPP MTB riboswitch RNAs (Thi C and Thi M). Specific Aim 3 We aim to test the hypothesis that pyrithiamine pyrophosphate (PTPP) can inhibit growth in MTB by binding to the TPP riboswitch.